tbuckley/cabot-search huggingface dataset:
POS0544 THE CONTRIBUTION OF THE 3RD AND 4TH BOOSTER BNT162B2 MRNA VACCINES TO PREVENT SEVERE COVID-19 AMONG AUTOIMMUNE INFLAMMATORY RHEUMATOID DISEASES (AIRD) PATIENTS DURING THE OMICRON OUTBREAKS
Authors: Y. Braun-Moscovici, M. Kaplan, M. Braun, R. Dr, D. Markovits, S. Giryes, V. Shataylo, R. Erlich, K. Toledano, F. Hasan, K. Dolnikov, Y. Tavor, A. Balbir-Gurman
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The 3<sup>rd</sup> booster of mRNA vaccines against SARS COV2 was highly efficient against delta variant but data regarding the efficacy of the 3<sup>rd</sup> and 4<sup>th</sup> boosters against the omicron variants, among AIRD pts are scarce. <h3>Objectives</h3> We aimed to assess the effect of the 3<sup>rd</sup> and 4<sup>th</sup> booster mRNA vaccines against SARS CoV2, in preventing severe COVID-19, in AIRD patients (pts) treated with immunomodulating drugs. <h3>Methods</h3> 212 pts (mean age(SD) 57(13), disease duration 11.2(7.4), who received the 3<sup>rd</sup> booster (Pfizer) were included in the study. We performed serology tests 24 weeks after the second dose of vaccine and 4-8 weeks after the 3<sup>rd</sup> booster. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay. The test was considered positive above 50 AU/ml. Data regarding COVID-19 infection during the 5<sup>th</sup> outbreak (omicron) were collected from the medical files. The length of observation period was defined as the time from the 3<sup>rd</sup> booster to the last hospital visit or COVID 19 diagnosis, whichever occurred first. <h3>Results</h3> The 3<sup>rd</sup> booster administration (Pfizer) significantly augmented the humoral response (from mean(SD) 1121(4723) AU/ml to 12153(13687)). 58 patients received the 4<sup>th</sup> booster and 18 the 5<sup>th</sup> booster. COVID-19 was diagnosed in 103 pts (49%) within mean(SD) 224.8(106.5) days after the 3<sup>rd</sup> booster vaccination. 109 pts remained free of disease during mean(SD) follow-up 230.6(133.9). Following the 4<sup>th</sup> booster, 26 (45%) out of 58pts contracted COVID-19 within mean(SD) 97.6(78.7) days after the vaccination. One 70 year old patient (vaccinated 3 times) died and 2 other pts (rituximab treated) had severe COVID-19. The IgG Ab titer after the 3<sup>rd</sup> booster was lower in pts who contracted COVID 19 compared to those uninfected (mean(SD), median 8777.9(11716.4),3475 AU/ml vs 15348.1(14649.1),10801, p=0.004). There were no statistically significant differences between the pts with COVID-19 and those without, regarding age, type of disease, treatment and humoral response 24 weeks after the 2<sup>nd</sup> vaccination. <h3>Conclusion</h3> Despite an enhanced humoral response obtained after the 3rd booster, 49% of AIRD pts vaccinated with 3 doses and 45% of pts vaccinated with 4 doses had COVID-19 during the omicron outbreaks. Higher humoral response to the 3<sup>rd</sup> booster was associated with a lower rate of COVID19. The booster vaccines conferred 99% protection against severe COVID-19. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0649 WHEN DOES OBESITY EXERT ITS EFFECT IN CONFERRING RISK OF DEVELOPING RA – A LARGE STUDY IN COHORTS OF SYMPTOMATIC PATIENTS AT RISK
Authors: Q. Dumoulin, D. Krijbolder, A. Willemze, P. De Jong, H. W. Van Steenbergen, A. Van der Helm – van Mil
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Case-control studies have identified body mass index (BMI) as a risk factor for development of rheumatoid arthritis (RA). However, it is unclear when BMI exerts its effect of increased risk, being either in the asymptomatic stage or in the symptomatic phase of Clinically Suspect Arthralgia (CSA) thereafter. <h3>Objectives</h3> To investigate this, we compared BMI of CSA-patients with the general population and we analyzed associations of BMI with progression to inflammatory arthritis (IA) within CSA-patients. <h3>Methods</h3> Firstly, 602 patients consecutively presenting with CSA were studied and followed during 2 years for development of IA. Their baseline BMI was compared to the mean BMI (corrected for age/gender) of the Dutch population (Statistics Netherlands,CBS,2012-2020). Secondly, cross-sectional associations between BMI and measures of inflammation, tender joint count (TJC-68) and C-reactive protein (CRP), were studied. Finally, the association of BMI and IA development was studied via cox-regression. Findings were validated in 295 additional comparable patients with CSA included in the SONAR (n=178) and TREAT EARLIER trial (placebo arm, n=117)); a pooled analysis was performed. <h3>Results</h3> CSA-patients had a higher mean BMI compared to the general population (26.5 vs 25.3 kg/m<sup>2</sup>, p&lt;0.001). Likewise, CSA-patients were more often obese (BMI ≥ 30 kg/m<sup>2</sup>) than the general population (22.3 vs 13.8%, Figure 1A); this applied to both ACPA-positive and ACPA-negative patients and was confirmed in the validation cohorts. At baseline, obese CSA-patients had higher TJC-68(β 1.26(1.04;1.52)) and CRP (1.37(1.20;1.57)) than CSA-patients with a normal weight. However, obese CSA-patients did not have an increased risk of IA development (HR 0.66(95%CI 0.39;1.11), Figure 1B). Similarly in the validation cohorts, higher BMI was not associated with RA-development (OR per point BMI 0.98(0.95;1.01) for both cohorts together, Figure 1C) <h3>Conclusion</h3> Obesity is more frequent in CSA compared to the general population. Moreover, obesity is associated with higher inflammation at presentation with CSA but did not entail a higher risk for progression from CSA to IA. Hence, obesity primarily seems to exert its effect in the asymptomatic risk-stage of RA-development. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0503 RISK OF CARDIOEMBOLIC ISCHAEMIC STROKE AMONG NEW USERS OF ORAL BISPHOSPHONATES: A NESTED CASE-CONTROL STUDY
Authors: S. Rodriguez-Martin, D. Barreira-Hernández, R. Mazzucchelli, M. Gil, A. García-Lledó, L. Izquierdo-Esteban, A. Pérez-Gómez, A. Rodríguez-Miguel, F. De Abajo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Bisphosphonates have been associated with atrial fibrillation, but studies carried out thus far have not shown that they are also associated with an increased risk of ischaemic stroke (IS). None, however, separated by IS subtype (cardioembolic vs non-cardioembolic). <h3>Objectives</h3> The present study aimed to test the hypothesis that use of oral bisphosphonates (oBs) increases specifically the risk of cardioembolic IS. <h3>Methods</h3> A nested case-control study was performed using the Spanish primary healthcare database BIFAP (period: 2002-2015). Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for exact age, sex, and index date (first recording of IS). The association of IS (overall and by subtype) with the use of oBs within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their corresponding 95%CI using conditional logistic regression. Only oBs initiators were considered. (Figure 1). <h3>Results</h3> A total of 4,568 cardioembolic IS cases (matched with 21,697 controls) and 9,213 non-cardioembolic IS cases (matched with 44,212 controls) were included. For cardioembolic IS, the use of oBs was associated with an AOR of 1.35(1.10-1.66), in a duration dependent manner (AOR≤1year=1.10;0.82-1.49; AOR&gt;1-3years=1.41;1.01-1.97; AOR&gt;3years=1.81;1.25-2.62; p for trend=0.001). Such increased risk only appeared when patients used concomitantly calcium supplements and was completely blunted by anticoagulants. No increased risk was observed for non-cardioembolic IS (AOR=1.03;0.88-1.21). <h3>Conclusion</h3> The long-term use of oBs with calcium supplements increases the risk of cardioembolic IS, while leaves materially unaffected the risk of non-cardioembolic IS. <h3>Acknowledgements</h3> The authors would like to acknowledge the excellent collaboration of the primary care physicians (general practitioners/paediatricians), as well as the support from the regional health administrations providing BIFAP data. <h3>Disclosure of Interests</h3> None Declared.
POS0380 PERFORMANCE OF EYE SIGN IN DIAGNOSING PATIENTS WITH NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: J. L. H. Shi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The featured alterations of eye sign has been reported (1) in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Whether eye sign can predict NPSLE remains unknown. <h3>Objectives</h3> To investigate the performances of potential predictors and predictive models utilizing eye sign in classifying NPSLE. <h3>Methods</h3> Patients (&gt;18 years) fulfilled the SLE diagnosis (2) were consecutively enrolled from 30 September 2016 to 30 September 2017. The diagnosis of NPSLE was evaluated and based on the consensus from rheumatologist, neurologist, radiologist and psychiatrist. Bulbar conjunctival microvascular changes in eye sign were performed and scored for all SLE patients by rheumatologist using our criteria. NP assessments were evaluating in all SLE patients by psychiatrist, including the mini-mental state examination (MMSE), self-rating anxiety scale (SAS), self-rating depression scale (SDS). Demographic and clinical data were compared between two groups and to identify potential predictors for NPSLE by using multivariable logistic regression analysis. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was used to evaluate the performance of the models in the prediction of NPSLE. <h3>Results</h3> 120 SLE patients were recruited (30 [24-41] years) including 30 NPSLE and 90 non-NPSLE. Totally 39 NP events were recorded in these NPSLE patients. NPSLE had higher disease activity (reflected as SLEDAI and ESR), more prevalence of positive antiphospholipid antibody (aPL), poorer NP assessments than non-NPSLE group. Eye sign examination showed NPSLE group had significantly changes of ramified loops, microangloma, wound spot, worse vascular tone and higher total score than non-NPSLE group. In multivariable logistic analysis, model 1 showed total score of eye sign was the only predictor for NPSLE; while in model 2, except for SLEDAI, specific items of ramified loops, microangloma and wound spot were predictors for NPSLE (Table 1). Predictive model 1 utilizing total score as predictor showed AUC of 0.933 with sensitivity of 83.3%, specificity of 93.3%; model 2 including SLEDAI, ramified loops, microangloma and wound spot demonstrated an AUC of 0.960 with sensitivity of 86.7%, specificity of 95.6% (Figure 1). <h3>Conclusion</h3> In conclusion, ramified loops, microangioma and wound spot in eye sign were independent predictors in addition to SLEDAI for patients with NPSLE. <h3>References</h3> [1]Wu R. Role of eye's sign in patients with neuropsychiatric disorders of systemic lupus erythematosus. Rheumatol Int. 2014 Apr;34(4):583-6. [2]Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0449 PRESENCE OF PERIODONTAL DISEASE AND THE INCIDENCE OF INFLAMMATORY ARTHRITIDES IN THE GENERAL POPULATION: DATA FROM THE UK BIOBANK
Authors: H. R. Yun, S. S. Ahn
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patients with inflammatory arthritides (IA) are now recognized to present with inflammation in the periodontium frequently. However, the association between signs of periodontal inflammation and IA onset has been poorly described in the existing literature. <h3>Objectives</h3> To investigate the association between periodontal disease and the development of inflammatory arthritides (IA) in the general population. <h3>Methods</h3> In total, 489,125 participants from the UK Biobank without a previous history of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) were enrolled. The primary outcome was the incidence of IA, which was a composite of RA, AS, and PsA according to the presence of periodontal disease based on self-reported oral health indicators. Multivariate Cox proportional hazard regression analyses using four different models were performed to assess the association between periodontal disease and IA development. <h3>Results</h3> In all, 86,905 and 402,220 individuals were categorized as with and without periodontal disease, respectively. Cox hazard analysis indicated that the presence of periodontal disease was an independent predictor of the occurrence of composite outcomes of IA, which was also consistent for RA and AS. Significant associations were found to be consistent in the four Cox models and were replicated even when different criteria were used to define periodontal disease. Subgroup analyses indicated that periodontal disease was associated with an increased RA risk in those aged &lt;60 years, and this risk was persistent for both male and female patients and for patients with seropositive/seronegative RA. <h3>Conclusion</h3> Self-reported periodontal disease is associated with IA incidence in participants included in the UK Biobank, particularly for RA and AS. Higher clinical attention and optimal dental care in patients with signs of periodontal disease may be recommended for early disease detection and for reducing this risk. <h3>References</h3> [1]Pisetsky DS, Ward MM. Advances in the treatment of inflammatory arthritis. Best Pract Res Clin Rheumatol 2012;26:251-61. [2]Hazes JM, Luime JJ. The epidemiology of early inflammatory arthritis. Nat Rev Rheumatol 2011;7:381-90. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0852 REAL LIFE DATA OF FILGOTINIB IN RHEUMATOID ARTHRITIS PATIENTS: DATA FROM ITALIAN GISEA REGISTRY
Authors: M. Fornaro, R. Caporali, C. Montecucco, A. Cauli, F. Conti, M. S. Chimenti, R. Gorla, F. Atzeni, A. Semeraro, E. Gremese, M. Sebastiani, M. Govoni, F. P. Cantatore, L. Santo, B. Frediani, G. Lapadula, G. Ferraccioli, F. Iannone
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In the age of targeted-synthetic disease-modifying antirheumatic drugs (tsDMARDs), filgotinib represents the last JAK inhibitor available in Europe for rheumatoid arthritis (RA). Filgotinib is characterized by predominantly inhibition of JAK1 and its efficacy and safety have been highlighted by phase 2/3 studies, but no real-life data in RA are currently available. <h3>Objectives</h3> The aim of this study was to evaluate the effectiveness and safety profile of filgotinib in real-life setting in RA patients included in Italian GISEA (Group for the Study of Early Arthritis) registry. <h3>Methods</h3> For this study, data from RA patients treated with filgotinib recorded in Italian GISEA registry were analysed. Disease activity scores and patients reported outcomes (PROs) were compared at baseline and six months follow-up using paired t-tests. The retention rate was estimated by the Kaplan-Meier method, while a cox regression model was used to search for possible factors influencing drug survival. <h3>Results</h3> One hundred and seventy-nine patients (female 89.4%, age 57.8±12 years, FR/ACPA+ 64.3%, current/former smoker 31.8%) included in GISEA registry started filgotinib for active RA. Most patients were taking filgotinib as second (23.5%) or further (43%) b/tsDMARDs line of treatment. Filgotinib was used in monotherapy in 66.5% of patients, while 52% were not on treatment with glucocorticoids (GCs) at baseline. All demographic and clinical data are reported in Table 1. A follow-up visit was available for 122 patients (mean time of first follow-up visit: 4±2 months). As shown in table 1, we observed a decrease of all disease activity scores and PROs. At first follow-up visit, 67.8% of patients were in remission/low disease activity according to CDAI and 65.4% according to SDAI. Kaplan-Meyer analysis highlighted that drug persistence was similar either in monotherapy or combination therapy (Figure 1a), and irrespective of GCs at baseline (Figure 1b). However, a better persistence was observed in RA patients on first line treatment with filgotinib (Figure 1c). Thirty-five patients stopped filgotinib during follow-up, 10 for lack of efficacy, 4 for loss of efficacy, 4 for adverse events, while for the remaining cases the cause of drug discontinuation was unknown. No major cardiovascular events were reported. Finally, univariate Cox-regression model showed that b/tsDMARD naïve patients had a lower risk of drug discontinuation (naïve vs other lines: HR 0.37, 95%CI 0.20-0.86). <h3>Conclusion</h3> In Italian real-life setting, filgotinib confirms a good effectiveness and safety profile. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0421 GLUCOSE TRANSPORTER 1 REGULATES MECHANICAL STRESS-ACTIVATED SUBCHONDRAL BONE FORMATION VIA THE SIGNAL TRANSDUCTION NETWORK OF CELLULAR ENERGY SENSOR, NAD+-DEPENDENT DEACETYLASE (SIRTUIN 1) AND OSTEOGENIC TRANSCRIPTION FACTOR, RUNT-RELATED TRANSCRIPTION FACTOR 2 (RUNX2), IN SUBCHONDRAL BONE TISSUE
Authors: K. Yudoh, S. Somemura, R. Karasawa
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Mechanical stress is an important factor affecting bone and cartilage tissue homeostasis in osteoarthritis (OA). We focused on the interaction among mechanical stress, glucose uptake via glucose transporter 1 (Glut1) and the cellular energy sensor sirtuin 1 (SIRT1) in energy metabolism, since it has been recognized that SIRT1, an NAD+-dependent deacetylase, may function as a master regulator of mechanical stress response as well as cellular energy metabolism Also, it has already been demonstrated that SIRT1 regulates the activity of the osteogenic transcription factor, runt-related transcription factor 2 (Runx2). <h3>Objectives</h3> Purpose of this study was to determine whether mechanical force affects the expression of factors regulating energy metabolism and transcription factors controlling subchondral bone formation and ossification in OA. <h3>Methods</h3> Comparative analyses of the expression of Glut1, SIRT1 and Runx2 in osteoblasts and chondrocytes were performed after mechanical loading of a 3D cell–collagen sponge construct. <h3>Results</h3> Mechanical loading increased osteoblast activity. Mechanical loading significantly increased the expression of Glut1, significantly decreased the expression of SIRT1 and increased the expression of Runx2 in osteoblasts in comparison with non-loaded osteoblasts. Incubation with Glut1 inhibitor blocked mechanical stress-induced changes in SIRT1 and Runx2 in osteoblasts. In contrast to osteoblasts, expressions of Glut1, SIRT1 and Runx2 in chondrocytes were decreased by loading. Over loading reduced chondrocyte activity (production of proteoglycan, type II collagen). <h3>Conclusion</h3> Our present study indicated that mechanical stress induced upregulation of Glut1, downregulation of SIRT1, and upregulation of Runx2 in osteoblasts, but not in chondrocytes. Since SIRT1 is known to negatively regulate Runx2 activity, mechanical stress-induced downregulation of SIRT1 may lead to upregulation of Runx2, resulting in osteoblast differentiation and bone formation. Incubation with Glut1 inhibitor blocked mechanical stress-induced changes in SIRT1 and Runx2 suggesting that Glut1 is necessary to mediate the responses of SIRT1 and Runx2 to mechanical loading. These results suggest that Glut1 regulates mechanical stress-activated subchondral bone formation and ossification via the signal transduction network of cellular energy sensors, sirtuin 1 and Runx2, in OA. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0499 DIFFERENCES IN FRACTURE RISK IN PATIENTS WITH DISCORDANT BONE MINERAL DENSITY IN THE HIPS: OBSERVATIONAL STUDY
Authors: A. Saeed, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoporosis is a condition characterised by low bone mineral density (BMD) and is associated with increased risk of fractures and subsequent increased morbidity and mortality. The usual sites of BMD measurements are either the non-dominant hip or the spine. The hip is used to predict fracture risk using the FRAX™ tool. Some patients have a different BMD as shown by their T scores in the contralateral hip. <h3>Objectives</h3> This study aimed to ascertain whether patients significantly discordant in their BMD on the contralateral hip have a different risk for fractures. <h3>Methods</h3> Data from a dual-energy x-ray absorptiometry (DEXA) scanner in the North West of England were used. Patients who were referred between 2004-2011 were studied. Patients had both hips scanned as well as risk factors and presence of fracture recorded. Data collected included age, sex, height, weight, BMI, history of fractures, rheumatoid arthritis status, smoking status, alcohol use and malabsorption. Those that had a BMD T-score difference of either greater than or equal +1 SD or -1SD were considered to have discordant hips. These two groups were compared using independent sample t-tests for continuous variables and chi-squared tests for categorical variables. Logistic models were then fitted to look at the odds of fracture in each group. <h3>Results</h3> The hip T-scores of 35759 patients were measured. Mean age was 62.17 (±12.78) with 84.16% being female. There were 15287 (42.75%) who had discordant hips. The odds ratio for the measured risk factors and the association with fracture are shown in <b>Table 1</b> below. <h3>Conclusion</h3> Hip discordance might be associated with adverse risk factors such as increased frequency of fractures. Measuring BMD of both hips could give a better estimate of future fracture risk. Further analysis of a subset from this group will be explored and presented. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.